Background: Paclitaxel is an effective chemotherapeutic agent for the treatment of cancer patients. Accumulating evidence suggests that circular RNAs (circRNAs) play critical roles in the occurrence and development of human cancers. However, there are few studies on interactions between paclitaxel and circRNAs in hepatocellular carcinoma (HCC). Materials and Methods: Cell counting kit-8 (CCK-8) assay and colony formation assay were conducted to determine cell proliferation. Cell apoptosis was assessed by flow cytometry. The expression levels of circRNA baculoviral IAP repeat-containing 6 (circ-BIRC6), microRNA-877-5p (miR-877-5p), and tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, zeta (YWHAZ) were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The mice xenograft model was established to investigate the roles of circ-BIRC6 and paclitaxel in vivo. The interaction between miR-877-5p and circ-BIRC6 or YWHAZ was predicted by bioinformatics analysis and verified by dual-luciferase reporter assay. Western blot assay was applied for measuring the protein expression of YWHAZ. Results: Paclitaxel suppressed HCC tumorigenesis through decreasing cell proliferation and accelerating apoptosis. Circ-BIRC6 and YWHAZ were upregulated, and miR-877-5p was downregulated in HCC tissues and cells. Paclitaxel treatment inhibited the expression of circ-BIRC6 and YWHAZ while promoted the expression of miR-877-5p. Circ-BIRC6 overexpression or miR-877-5p interference reversed the inhibitory effect of paclitaxel on HCC tumorigenesis. Moreover, miR-877-5p could specially bind to YWHAZ, and its knockdown abated the suppressive effect of circ-BIRC6 depletion on HCC tumorigenesis. Additionally, YWHAZ was identified as a direct target of miR-877-5p. Besides, circ-BIRC6 functioned as a molecular sponge of miR-877-5p to regulate YWHAZ expression. Conclusion: Paclitaxel limited HCC tumorigenesis via modulating circ-BIRC6/miR-877-5p/YWHAZ axis, providing a novel therapeutic approach for the treatment of HCC.
Background: Baicalein has a significant anti-cancerous function in the treatment of cervical cancer (CC). Its functional mechanism regarding circular RNA (circRNA) hippocampus abundant transcript 1 (circHIAT1) and microRNA-19a-3p (miR-19a-3p) was explored in this research. Methods: CC cell viability and colony formation were determined using Cell Counting Kit-8 (CCK-8) and colony formation assay. Cell cycle progression and apoptosis were analyzed via flow cytometry. Protein markers of cell cycle, apoptosis and protein kinase B/mammalian target of rapamycin (AKT/mTOR) pathway were detected by Western blot. CircHIAT1 and miR-19a-3p levels were assayed through the quantitative real-time polymerase chain reaction (qRT-PCR). The interaction between circHIAT1 and miR-19a-3p was validated by dual-luciferase reporter and RNA pull-down assays. In vivo experiment was performed by xenograft model. Results: CC cell growth and cell cycle progression were repressed while apoptosis was enhanced by baicalein. MiR-19a-3p was downregulated in baicalein-treated CC cells and miR-19a-3p overexpression lightened the baicalein-induced CC progression inhibition. Moreover, circHIAT1 was found to be a sponge of miR-19a-3p in CC cells. Baicaleininduced cell growth inhibition, cell cycle arrest and apoptosis promotion were neutralized by knockdown of circHIAT1 via targeting miR-19a-3p. Baicalein acted on the circHIAT1/miR-19a-3p to inactivate AKT/mTOR pathway. Baicalein also reduced CC tumor growth in vivo via regulating the levels of circHIAT1 and miR-19a-3p. Conclusion: These findings demonstrated that the inhibitory function of baicalein in CC progression was dependent on the repression of AKT/mTOR pathway by upregulating circHIAT1 to sponge miR-19a-3p, showing a specific mechanism for baicalein in CC.
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